Children have excellent defenses against oral infections. They lose deciduous teeth and erupt permanent teeth without infections and rarely get periodontal disease even in the presence of plaque. This project will investigate the role without infections and rarely get periodontal disease even in the presence of plaque. This project will investigate the role of beta- defensins, a newly recognized family of small, cationic peptides with anti- microbial activity, in oral health and disease susceptibility. Oral epithelia are constantly exposed to microbial challenges that lead to bacterially induced gingivitis, periodontal diseases and other infections. Recent findings show that mucosal epithelial cells, including gingival epithelial are the source of beta-defensins. These peptides are predicted to function as a first line of host defense against microbial pathogens and are now recognized as part of the innate or non-adaptive hot defense system. Two beta-defensin peptides, hBD-1 and hBD-2, are expressed and differentially regulated in gingival epithelial cells. This proposal is based on the hypotheses that (1) beta- defensin peptides produced by oral epithelial cells play an important role in determining the outcome of the host pathogen interaction at the oral mucosal barrier, (2) these peptides may be important in the normal protective function of the oral mucosa during development, and (3) variation in individual expression of these peptides may be a contributing factor to susceptibility to specific oral disorders in children and adults. These peptides have future potential for prevention and treatment of oral microbial disorders, including periodontal disease, caries, recurrent candidal infections, and oral mucositis. The goals of this study encompass basic investigations and applied studies. We seek to understand the regulation of beta-defensin mRNA expression emphasizing epithelial differentiation and cell signaling pathways for expression upon stimulation by examples of commensal and pathogenic organisms, and by a two-component biofilm; to explore the relationship of beta-defensin expression and that of inflammatory cytokines; to determine beta-defensin expression in non- invasively collected oral samples from children, and to explore variation in defensin expression as a function of age and to test the hypothesis that defensin expression has correlated with oral health status in test populations in collaboration with other Comprehensive Center investigators.